Comparison of Recipient Outcomes After Kidney Transplantation: In-House Versus Imported Deceased Donors S.Y. Lima, J.G. Gwonb, M.G. Kimc, and C.W. Jungb,* a Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; bDepartment of Surgery, Korea University Anam Hospital, Seoul, Republic of Korea; and cDepartment of Internal Medicine, Korea University Anam Hospital, Seoul, Republic of Korea
ABSTRACT Background. Increased cold ischemia time in cadaveric kidney transplants has been associated with a high rate of delayed graft function (DGF), and even with graft survival. Kidney transplantation using in-house donors reduces cold preservation time. The purpose of this study was to compare the clinical outcomes after transplantation in house and externally. Methods. We retrospectively reviewed the medical records of donors and recipients of 135 deceased-donor kidney transplantations performed in our center from March 2009 to March 2016. Results. Among the 135 deceased donors, 88 (65.2%) received the kidneys from in-house donors. Median cold ischemia time of transplantation from in-house donors was shorter than for imported donors (180.00 vs 300.00 min; P < .001). The risks of DGF and slow graft function were increased among the imported versus in-house donors. Imported kidney was independently associated with greater odds of DGF in multivariate regression analysis (odds ratio, 4.165; P ¼ .038). However, the renal function of recipients at 1, 3, 5, and 7 years after transplantation was not significantly different between the 2 groups. Conclusions. Transplantation with in-house donor kidneys was significantly associated with a decreased incidence of DGF, but long-term graft function and survival were similar compared with imported donor kidneys.
D
ECEASED-DONOR kidneys are usually accompanied by an immediate renal ischemic event due to cold ischemia time (CIT) [1]. CIT refers to the time between initial cold perfusion during organ retrieval and the start of the surgical procedure for blood vessel anastomosis to the recipient. It plays a crucial role in the success of deceaseddonor kidney transplantation (DDKT). The association between prolonged CIT and adverse graft and patient outcomes is well established in kidney transplantation from deceased donors [1,2]. Allocation of deceased-donor kidneys in Korea is strictly regulated by the Korean Network for Organ Sharing. In kidney grafts imported from outside of the local hospital, CIT is prolonged owing to the time required to transport the organ to the accepting center. The aim of the present study ª 2018 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 50, 1025e1028 (2018)
was to compare the clinical outcomes of imported versus in-house grafts in patients undergoing DDKT. METHODS Study Population We retrospectively analyzed the medical records of the donors and recipients for the 135 DDKT procedures performed at the Korea University Anam Hospital from March 2009 to March 2016. The study received full approval from the Korea University Anam
*Address correspondence to Cheol Woong Jung, MD, PhD, Professor, Korea University Medical College, 5Ka, Anam-Dong, Sungbuk-Gu Korea University Anam Hospital 136-705, Seoul, Republic of Korea. E-mail:
[email protected] 0041-1345/18 https://doi.org/10.1016/j.transproceed.2018.01.035
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Table 1. Baseline Characteristics of Donors and Recipients In-House (n ¼ 88)
Imported (n ¼ 47)
P Value
46.50 69 (78.4) 1.90 1.67
55.00 18 (64.3) 2.20 1.60
.047 .133 .182 .323
24 (27.9) 11 (12.8) 45 (64.3) 49.50 54 (61.4) 1.10
14 (31.1) 10 (22.2) 17 (54.8) 53.00 31 (66.0) 4.20
.701 .162 .368 .662 .599 .003 <.005
24 (27.2) 36 (40.9) 28 (31.9) 180
16 (36.4) 14 (31.8) 14 (31.8) 300
Characteristic
Donor age (y) Donor sex male Peak creatinine (mg/dL) Final creatinine (mg/dL) Underlying illness of donors Hypertension Diabetes AKI donor Recipient age (y) Recipient sex male Donor recipient BMI (kg/m2) HLA mismatch 3 4 5 Cold ischemia time (min)
<.001
Note. Data are expressed as median or n (%). Abbreviations: AKI, acute kidney injury; BMI, body mass index.
Hospital’s Institutional Review Board, which waived the need for informed consent because the study did not infringe on patient privacy or health status.
Table 2. Clinical Outcomes Following In-House and Imported Donor Kidney Transplantation, n (%) Outcome
Acute rejection ACMR AAMR ACMR þ AAMR Graft function Intermediate graft function Slow graft function Delayed graft function Graft failure
In-House (n ¼ 88)
Imported (n ¼ 47)
10 (11.4) 8 (9.1) 7 (8.0)
8 (17.0) 5 (10.6) 6 (12.8)
P Value
.168
.011 44 17 6 7
(70.4) (21.1) (8.5) (8.0)
18 9 8 5
(41.4) (31.0) (27.6) (10.6)
.602
Abbreviations: ACMR, acute cell-mediated rejection; AAMR, acute antibodymediated rejection.
respectively. Their peak and final sCr levels before graft harvest were 1.90 mg/dL and 1.67 mg/dL versus 2.20 mg/dL and 1.60 mg/dL, respectively (Table 1). The proportion of patients with AKI diagnosis, and the severity of AKI as defined by KDIGO staging were not different according to donor location. No significant differences were observed in donors’ age or underlying illness. However, compared with in-house donor kidneys, imported kidneys had significantly longer CITs (median 180 min vs. 300 min; P < .001). The 2
Data Collection and Definitions Based on medical records, the following variables of recipient data were assessed: age, sex, height, weight, history of hypertension or diabetes, and initial, peak, and final serum creatinine (sCr) levels. We also collected data from the medical records of recipients on immunosuppressant use, sCr, and history of dialysis. Estimated glomerular filtration rate (eGFR) was calculated from sCr values with the use of the Modification of Diet in Renal Disease formula [3]. Acute kidney injury (AKI) was defined according to the Kidney Disease Improving Global Outcomes staging [4] or as an increase of 1.5 mg/dL above initial sCr level for patients without recorded baseline renal status. Based on recipient data for graft function in the immediate postoperative period, delayed graft function (DGF) was defined as dialysis requirement during the 1st week after transplantation, slow graft function (SGF) as a serum creatinine level of 3.0 mg/dL at post-transplantation day 5 without the need for dialysis, and immediate graft function as absence of DGF or SGF [5]. Graft biopsy results were reviewed, and cases reported as acute rejection were defined as biopsy-proven acute rejection, regardless of the type of rejection.
Statistical Analysis The numeric data of the 2 groups were compared with the use of the Student t test or the Mann-Whitney test. Categoric data were compared with the use of the chi-square test or Fisher exact test, as appropriate. Multiple logistic models were used for analyzing prognostic factors for outcome. All statistical analyses were performed with the use of SPSS software version 21.0 (Chicago, Ill, USA). A P value < .05 was considered to be statistically significant.
RESULTS Baseline Characteristics
A total of 88 and 47 patients received kidney transplantations from in-house and imported kidney donors,
Fig 1. Differences in renal function between in-house and imported donor groups at 1, 3, 5, and 7 years after transplantation. Abbreviations: Cr, creatinine; eGFR, estimated glomerular filtration rate.
COMPARISON OF RECIPIENT OUTCOMES AFTER KT
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Table 3. Multivariate Logistic Regression Analysis for Predicting Delayed Graft Function Univariate Analysis Variable
Age Diabetes Donor age AKI donor Donor creatinine (mg/dL) Imported donor (vs in-house donor)
Odds Ratio (95% CI)
1.025 2.812 1.039 4.500 1.463 4.127
(0.969e1.085) (0.639e12.379) (0.987e1.095) (0.947e21.373) (0.726e2.948) (1.284e13.260)
Multivariate Analysis P Value
.380 <.171 .137 .058 .287 .017
Odds Ratio (95% CI)
P Value
9.565 (1.132e80.809)
.038
4.165 (1.132e15.598)
.034
Abbreviations: AKI, acute kidney injury; CI, confidence interval.
groups were similar regarding other recipient characteristics, such as recipient age and sex. Clinical Outcomes
DGF occurred in 27.6% of imported versus 8.5% in-house DDKT (P ¼ .011), and immediate graft function occurred in 70.4% of imported versus 41% of in-house kidney recipients. No differences were found in the incidences of acute rejection and graft failure in recipients of imported kidney compared with in-house donor kidneys (Table 2). One-, 3-, 5-, and 7-year renal functions were similar in both groups (Fig 1). To evaluate the independent risk factors predicting the development of DGF, a multivariate analysis was performed with the use of a logistic regression model (Table 3). Transplantation with imported kidney was found to be associated with independent risk factors of DGF after DDKT (odds ratio, 4.165; P ¼ .034). Transplantation of kidneys from donors with AKI was also found by logistic regression analysis to facilitate the prediction of DGF (odds ratio, 9.565; P ¼ .038). However, none of these was able to accurately predict long-term graft failure. DISCUSSION
In this study, the incidences of DGF and SGF were higher in patients who received imported kidney compared with in-house kidney transplants. Furthermore, transplantation with an imported kidney was an independent risk factor for the occurrence of DGF. The use of an imported kidney was also associated with a high incidence of acute rejection. However, graft function at 1, 3, 5, and 7 years after transplantation did not differ between the imported and in-house kidney recipients. The donors and recipients in each group were similar regarding baseline clinical variables known to affect longterm graft survival rates. The only clinical variable that was significantly different between the 2 groups was the duration of CIT, which was obviously longer for the group transplanted with imported kidneys. Longer CIT might affect the imported kidney’s susceptibility to DGF and SGF. Experimental studies in kidney transplantation demonstrated that prolonged ischemia is closely related to organ malfunction [1]. Previous studies have also shown that increased duration of CIT in DDKT may result in DGF and even decreased graft survival [6e8]. Similarly, Kayler et al evaluated paired kidneys that were derived from the same donor transplanted
in different recipients with different CITs [9,10]. They found that DGF was more likely between pairs with greater CIT, but graft survival was not different between recipients with higher CIT compared with paired donor recipients with lower CIT. Our CITs for imported and in-house donors were 300 minutes and 180 minutes, respectively, which significantly raised the DGF rate in imported grafts. Consistently with previous findings [11], kidney transplantation from AKI donors was independently associated with DGF in the present study. The higher rates of DGF in patients with AKI affect the association between the use of imported kidneys and DGF development. Therefore, we performed multivariate regression analysis and found that the use of an imported kidney remains a significant risk factor for DGF development even after adjusting for AKI donor and other clinical and demographic factors. Moreover, in subgroup analysis of patients who received kidneys from AKI donors, longer CIT and high incidence of DGF were observed in the imported donor group compared with the in-house donor group. In addition to the effect of CIT on DGF, we evaluated the impact of imported donor kidneys on graft function up to 7 years after transplantation. No statistically significant differences in sCr and eGFR were observed up to 7 years after transplantation between imported and inehouse kidneys. Prolonged CIT impairs kidney function in the early post-transplantation period, and therefore its impact on longterm graft function and graft survival is controversial. Recently, Debout et al found a direct relationship between each additional hour of CIT and the risk of graft failure [12]. Kidney sharing in Korea occurs within a small region with a mean CIT <36 hours. Thus, a relatively short CIT in our study might have contributed to the conflicting results. In conclusion, transplantation with an in-house donor kidney was significantly associated with decreased incidence of DGF. However, long-term graft function and survival were similar compared with imported donor kidneys. REFERENCES [1] Siedlecki A, Irish W, Brennan DC. Delayed graft function in the kidney transplant. Am J Transplant 2011;11:2279e96. [2] Ponticelli CE. The impact of cold ischemia time on renal transplant outcome. Kidney Int 2015;87:272e5. [3] Stevens LA, Coresh J, Feldman HI, et al. Evaluation of the modification of diet in renal disease study equation in a large diverse population. J Am Soc Nephrol 2007;18:2749e57.
1028 [4] Section 2: AKI definition. Kidney Int Suppl 2012;2:19e36. [5] Johnston O, O’Kelly P, Spencer S, et al. Reduced graft function (with or without dialysis) vs immediate graft functionda comparison of long-term renal allograft survival. Nephrol Dial Transplant 2006;21:2270e4. [6] Kayler LK, Srinivas TR, Schold JD. Influence of CIT-induced DGF on kidney transplant outcomes. Am J Transplant 2011;11: 2657e64. [7] Kayler L, Yu X, Cortes C, Lubetzky M, Friedmann P. Impact of cold ischemia time in kidney transplants from donation after circulatory death donors. Transplant Direct 2017;3:e177. [8] van der Vliet JA, Warle MC. The need to reduce cold ischemia time in kidney transplantation. Curr Opin Organ Transplant 2013;18:174e8.
LIM, GWON, KIM ET AL [9] Kayler LK, Magliocca J, Zendejas I, Srinivas TR, Schold JD. Impact of cold ischemia time on graft survival among ECD transplant recipients: a paired kidney analysis. Am J Transplant 2011;11:2647e56. [10] Giessing M, Fuller TF, Friedersdorff F, et al. Comparison of first and second kidney transplants from the same deceased donor. Nephrol Dial Transplant 2010;25:4055e61. [11] Xia Y, Friedmann P, Cortes CM, Lubetzky ML, Kayler LK. Influence of cold ischemia time in combination with donor acute kidney injury on kidney transplantation outcomes. J Am Coll Surg 2015;221:532e8. [12] Debout A, Foucher Y, Trebern-Launay K, et al. Each additional hour of cold ischemia time significantly increases the risk of graft failure and mortality following renal transplantation. Kidney Int 2015;87:343e9.